Current Organic Chemistry - Volume 20, Issue 1, 2016

Developments in the synthesis of bicyclo[n.1.0]alkanes by lithium 2,2,6,6-tetramethylpiperidide-induced intramolecular cyclopropanation of unsaturated terminal epoxides are reviewed. The main alternative intramolecular cyclopropanation strategies are also briefly discussed to put the epoxide chemistry in perspective. Terminal epoxide (or chlorohydrin) precursors possessing a tethered alkene undergo intramolecular cyclopropanation with complete stereoselectivity and in generally good to excellent yields to give cyclopropyl alcohols; application of this cyclopropanation methodology in the synthesis of natural products is also reviewed.

Diazocarbonyl compounds have broad applications in organic chemistry research. They can be applied to synthesize epoxides and aziridines, which are valuable small heterocycles. This review discusses selected examples that produce epoxides and aziridines from diazocarbonyl compounds under catalytic conditions and in a selective fashion.

β-Lactam, with its unique four-membered ring structure, is an irreplaceable motif in antibacterial medicines, and the diversity synthesis of monocyclic β-lactam becomes a very effective approach for the discovery of new pharmacological properties and bioactivities. During the last few decades, efforts have been spent on the chemical synthesis of β-lactams, including approaches via metal catalysis and organocatalysis. In this review, progresses in catalytic intramolecular metal carbene insertion reaction for the β-lactams structure construction during the last two decades are demonstrated, which emphasize the chemo-, diastereo- and enantioselectivity advances in these transformations of diazo compounds with structural diversity. And a few of selected initial researches led to significant advances are also mentioned in this article.

Metal carbene-involved C-H insertion reaction is among the most useful and efficient method for the construction of C-C bonds. While C(sp3)-H insertion and C(sp2)-H insertion have been intensively studied during the past several decades, C(sp)-H insertion of terminal alkynes with metal carbenes has only received great attention from the synthetic community recently. This cross-coupling reaction between terminal alkynes with different metal carbene precursors offers a versatile strategy for the synthesis of different types of alkynes or allenes, which are very useful synthetic intermediates in organic synthesis. This type of cross-coupling reaction, in which a migratory insertion step of alkynylsubstituted metal carbene species is generally involved, also offers new opportunities for the development of related cascade or multicomponent reactions.

Dirhodium(II) catalysts have proven effectiveness in controlling selectivity in metal carbene reactions of diazocarbonyl compounds. Over the years many dirhodium(II) paddlewheel derivatives with chiral ligands have been advanced, but three structural classes have emerged as being most effective for inducing high stereocontrol: chiral dirhodium carboxamidates derived from cyclic chiral carboxamides and chiral dirhodium carboxylic acids derived from sybstituted chiral prolinates or from phthalimide-protected α-amino acids. This review focuses on describing which of these classes of chiral dirhodium(II) catalysts have provided the highest levels of stereocontrol in intramolecular and intermolecular reactions of diazoacetates, diazoacetoacetates and diazomalonates, vinyl- and aryldiazoacetates, and enoldiazoacetates. Assessment is taken from published results that compare catalyst results for cyclopropanation, cyclopropenation, C-H insertion, ylide formation and reactions, as well as cycloaddition reactions, especially [3+3]- and [4+3]-cycloaddition.

Carbene and metal carbenoid species, originally viewed as too reactive to be useful for complex molecule synthesis, have now emerged as attractive intermediates for the construction of highly functionalized heterocyclic compounds. A popular route to metal carbenoids involves the decomposition of diazo starting materials, using various transition metals. In this review we highlight some of the utilities of metal carbenoids in the synthesis of biologically-active or natural product-like compounds. Some of the reaction classes that feature prominently in these syntheses of alkaloids, described here, involve heteroatom/C-H insertion or cyclopropanation and 1,3-dipolar cycloadditions. The facile constructions of fused ring systems via cascade reactions that encompass carbenoids are also discussed.

Recently, non-diazo carbene precursors have attracted more and more interest because of the apparent safety reason. As one of the most reliable and useful non-diazo carbenoid precursors, enynal/enynone can give rise to furyl- or pyrylium-carbene, which has be applied in a wide range of carbene-transfer reactions, such as cyclopropanation, C-H and X-H insertion, 1,3-dipolar cycloaddition and ylide formation reaction.